This invention is related to the field of compounds having fungicidal activity and processes to produce and use same.
Our history is riddled with outbreaks of fungal diseases that have caused widespread human suffering. One need look no further than the Irish potato famine, which occurred from 1845 to 1860, where an estimated 1,000,000 people died, and an estimated 1,500,000 emigrated, to see the effects of a fungal disease.
Fungicides are compounds, of natural or synthetic origin, which act to protect plants against damage caused by fungi. Current methods of agriculture rely heavily on the use of fungicides. In fact, some crops cannot be grown usefully without the use of fungicides. Using fungicides allows a grower to increase the yield and the quality of the crop and consequently, increase the value of the crop. In most situations, the increase in value of the crop is worth at least three times the cost of the use of the fungicide. However, no one fungicide is useful in all situations. Consequently, research is being conducted to produce fungicides that are safer, that have better performance, that are easier to use, and that cost less.
In light of the above, the inventors provide this invention.
It is an object of this invention to provide compounds that have fungicidal activity.
It is an object of this invention to provide processes that produce compounds that have fungicidal activity.
It is an object of this invention to provide processes that use compounds that have fungicidal activity.
In accordance with this invention, processes to produce and processes to use compounds having a general formula according to formula one, and said compounds are provided.
While all the compounds of this invention have fungicidal activity, certain classes of compounds may be preferred for reasons such as, for example, greater efficacy, or ease of synthesis.
Throughout this document, all temperatures are given in degrees Celsius and all percentages are weight percentages, unless otherwise stated. The term xe2x80x9cMexe2x80x9d refers to a methyl group. The term xe2x80x9cEtxe2x80x9d refers to an ethyl group. The term xe2x80x9cPrxe2x80x9d refers to a propyl group. The term xe2x80x9cppmxe2x80x9d refers to parts per million. The term, xe2x80x9cpsixe2x80x9d refers to pounds per square inch.
The compounds of this invention have a formula according to formula one. 
In formula one:
A1, A2, A3, and A4 are independently selected from the group consisting of hydro (xe2x80x94H), halo (xe2x80x94F, xe2x80x94Cl, xe2x80x94Br, and xe2x80x94I), and methyl (xe2x80x94CH3);
E is selected from the group consisting of aza (xe2x80x94Nxe2x95x90) and methine (xe2x80x94CHxe2x95x90);
G is selected from the group consisting of oxo (Oxe2x95x90) and thioxo (Sxe2x95x90);
J is selected from the group consisting of oxy (xe2x80x94Oxe2x80x94), amino (xe2x80x94NHxe2x80x94) and alkylamino (xe2x80x94NT1xe2x80x94) where T1 is an alkyl group having 1 to 6 carbon atoms;
L1, L2, and L3 are independently selected from the group consisting of hydro (xe2x80x94H), halo (xe2x80x94F, xe2x80x94Cl, xe2x80x94Br, and xe2x80x94I), cyano (xe2x80x94CN), methyl (xe2x80x94CH3), and mono, di, and trihalomethyl;
M is selected from the group consisting of thio (xe2x80x94Sxe2x80x94), sulfinyl (xe2x80x94S(xe2x95x90O)xe2x80x94), and sulfonyl (xe2x80x94S(xe2x95x90O)2xe2x80x94); and
Q is selected from the group consisting of aryl (xe2x80x94Aryl), substituted aryl (xe2x80x94SAryl), heteroaryl (xe2x80x94HAryl), and substituted heteroaryl (xe2x80x94SHAryl), where xe2x80x9carylxe2x80x9d or xe2x80x9cPhxe2x80x9d refers to a phenyl group and where xe2x80x9cheteroarylxe2x80x9d refers to pyridyl, pyridinyl, pyrazinyl or pyridazinyl, and where said SAaryl and SHAryl have substituents that are independently selected from the group consisting C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, halo, nitro, carbo-C1-C6 alkoxy, or cyano, arylalkyl, alkanoyl, benzoyl, amino, and substituted amino, preferably, hydro (xe2x80x94H), C1-C6 alkyls, arylalkyl, alkanoyl, benzoyl, amino, and substituted amino where said substituted amino has substituents that are independently selected from the group consisting of hydro (xe2x80x94H), alkyl, arylalkyl, alkanoyl, benzoyl, and amino.
The term xe2x80x9calkylxe2x80x9d, xe2x80x9calkenylxe2x80x9d, or xe2x80x9calkynylxe2x80x9d refers to a unbranched or branched chain carbon group.
The term xe2x80x9calkoxyxe2x80x9d refers to a unbranched or branched chain alkoxy group.
The term xe2x80x9chaloalkylxe2x80x9d refers to a unbranched or branched alkyl group substituted with one or more halo atoms. The term xe2x80x9chaloalkoxyxe2x80x9d refers to an alkoxy group substituted with one or more halo atoms.
In general, these compounds can be produced by reacting a compound of formula two with a compound of formula three under suitable reaction conditions. 
In formulas two and three, the variables are the same as in formula one and R is selected from the group consisting of halo (xe2x80x94F, xe2x80x94Cl, xe2x80x94Br, and xe2x80x94I), and alkylsulfonyl (xe2x80x94S(xe2x95x90O)2xe2x80x94T2) where T2 is an alkyl group having from 1 to 6 carbon atoms.
In general, suitable reaction conditions include, the use of a strong base such as, for example, sodium hydride or potassium tert-butoxide, in a polar aprotic medium, such as, for example, tetrahydrofuran, diethylether, or dimethylsulfoxide, at temperatures that range from about 0 to about 100xc2x0 C.
In general, these compounds can be used in a variety of ways. These compounds are preferably applied in the form of a formulation comprising one or more of the compounds with a phytologically-acceptable carrier. Concentrated formulations can be dispersed in water, or another liquid, for application, or formulations can be dust-like or granular, which can then be applied without further treatment. The formulations are prepared according to procedures which are conventional in the agricultural chemical art, but which are novel and important because of the presence therein of one or more of the compounds.
The formulations which are applied most often are aqueous suspensions or emulsions. Such water-soluble, water suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. The present invention contemplates all vehicles by which one or more of the compounds can be formulated for delivery and use as a fungicide.
As will be readily appreciated, any material to which these compounds can be added may be used, provided they yield the desired utility without significant interference with the activity of these compounds as antifungal agents.
Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of one or more of the compounds, an inert carrier and surfactants. The concentration of the compound in the wettable powder is usually from about 10% to about 90% w/w, more preferably about 25% to about 75% w/w. In the preparation of wettable powder formulations, the compounds can be compounded with any of the finely divided solids, such as prophyllite, talc, chalk, gypsum, Fuller""s earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier is ground or mixed with the compounds in a volatile organic solvent. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, include sulfonated lignins, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants, such as ethylene oxide adducts of alkyl phenols.
Emulsifiable concentrates of the compounds comprise a convenient concentration, such as from about 10% to about 50% w/w, in a suitable liquid. The compounds are dissolved in an inert carrier, which is either a water miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.
Emulsifiers which can be advantageously employed herein can be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil soluble salts or sulphated polyglycol ethers and appropriate salts of phosphated polyglycol ether.
Representative organic liquids which can be employed in preparing the emulsifiable concentrates of the present invention are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, and the methyl ether of triethylene glycol. Mixtures of two or more organic liquids are also often suitably employed in the preparation of the emulsifiable concentrate. The preferred organic liquids are xylene, and propyl benzene fractions, with xylene being most preferred. The surface active dispersing agents are usually employed in liquid formulations and in the amount of from 0.1 to 20 percent by weight of the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
Aqueous suspensions comprise suspensions of one or more water-insoluble compounds, dispersed in an aqueous vehicle at a concentration in the range from about 5% to about 50% w/w. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other ingredients, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle. It is often most effective to grind and mix at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.
The compounds may also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations usually contain from about 0.5% to about 10% w/w of the compounds, dispersed in an inert carrier which consists entirely or in large part of coarsely divided attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in. the range of from about 0.5 to about 3 mm. Such formulations may also be prepared by making a dough or paste of the carrier and the compound, and crushing and drying to obtain the desired granular particle.
Dusts containing the compounds are prepared simply by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% w/w of the compounds.
The formulations may contain adjuvant surfactants to enhance deposition, wetting and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will vary from 0.01 percent to 1.0 percent v/v based on a spray-volume of water, preferably 0.05 to 0.5%. Suitable adjuvant surfactants include ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines and blends of surfactants with mineral or vegetable oils.
The formulations may optionally include combinations which can comprise at least 1% of one or more of the compounds with another pesticidal compound. Such additional pesticidal compounds may be fungicides, insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.
The present invention includes within its scope methods for the control or prevention of fungal attack. These methods comprise applying to the locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidal amount of one or more of the compounds. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds are useful in a protectant or eradicant fashion. The compounds are applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots, seeds or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials are applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrates, or emulsifiable concentrates. These materials are conveniently applied in various known fashions.
The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants, or with wood, paint, leather or carpet backing.
In particular, the compounds effectively control a variety of undesirable fungi which infect useful plant crops. Activity has been demonstrated for a variety of fungi, including for example the following representative fungi species: Downy Mildew of Grape (Plasmopara viticolaxe2x80x94PLASVI); Late Blight of Tomato and Potato (Phytophthora infestansxe2x80x94PHYTIN); Apple Scab (Venturia inaequalisxe2x80x94VENTIN); Brown Rust of Wheat (Puccinia reconditaxe2x80x94PUCCRT); Stripe Rust of Wheat (Puccinia striiformisxe2x80x94PUCCST); Rice Blast (Pyricularia oryzaexe2x80x94PYRIOR); Cercospora Leaf Spot of Beet (Cercospora beticolaxe2x80x94CERCBE); Powdery Mildew of Wheat (Erysiphe graminisxe2x80x94ERYSGT); Leaf Blotch of Wheat (Septoria triticixe2x80x94SEPTTR); Sheath Blight of Rice (Rhizoctonia solanixe2x80x94RHIZSO); Eyespot of Wheat (Pseudocercosporella herpotrichoidesxe2x80x94PSDCHE); Brown Rot of Peach (Monilinia fructicolaxe2x80x94MONIFC); and Glume Blotch of Wheat (Septoria nodorumxe2x80x94LEPTNO).
It will be understood by those in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.
The compounds have broad ranges of efficacy as fungicides. The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.
The compounds are effective in use with plants in a disease inhibiting and phytologically acceptable amount. The term xe2x80x9cdisease inhibiting and phytologically acceptable amountxe2x80x9d refers to an amount of a compound which kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 1 to about 1000 ppm, with 10 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.1 to 0.45 grams per square meter g/m2).